Recombinant human collagen-based microspheres mitigate cardiac conduction slowing induced by adipose tissue-derived stromal cells

• Published in: PloS one 2017-08, Vol.12 (8), p.e0183481-e0183481
• Main Authors: Smit, Nicoline W, Ten Sande, Judith N, Parvizi, Mojtaba, van Amersfoorth, Shirley C M, Plantinga, Josée A, van Spreuwel-Goossens, Carolien A F M, van Dongen, Elisabeth M W M, van Dessel, Pascal F H M, Kluijtmans, Sebastianus G J M, Meijborg, Veronique M F, de Bakker, Jacques M T, Harmsen, Martin C, Coronel, Ruben
• Format: Article
• Language: English
• Subjects: Action Potentials; Adipose tissue; Adipose Tissue - cytology; Adipose Tissue - ultrastructure; Animals; Autocrine signalling; Biology; Biology and Life Sciences; Biomaterials; Biomedical materials; Body fat; Cardiac muscle; Cardiology; Cardiomyocytes; Collagen; Collagen - administration & dosage; Conditioning; Conduction; Connexin 43 - metabolism; Culture Media, Conditioned; Fibroblasts; Genetic aspects; Heart; Heart attacks; Heart diseases; Heterogeneity; Human behavior; Humans; Infarction; Ischemia; Manufacturing; Medicine and Health Sciences; Mesenchymal stem cells; Microelectrodes; Microscopy, Electron, Scanning; Microspheres; Monolayers; Myocardial infarction; Myocytes; Myocytes, Cardiac - physiology; Neonates; Paracrine signalling; Pathology; Peptides; Physical Sciences; Physiological aspects; Rats; Recombinant Proteins - administration & dosage; Research and Analysis Methods; Retarding; Retention; Stem cells; Stromal cells; Stromal Cells - cytology; Stromal Cells - ultrastructure; Studies; Velocity; Ventricle
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0183481

Stem cell therapy to improve cardiac function after myocardial infarction is hampered by poor cell retention, while it may also increase the risk of arrhythmias by providing an arrhythmogenic substrate. We previously showed that porcine adipose tissue-derived-stromal cells (pASC) induce conduction slowing through paracrine actions, whereas rat ASC (rASC) and human ASC (hASC) induce conduction slowing by direct coupling. We postulate that biomaterial microspheres mitigate the conduction slowing influence of pASC by interacting with paracrine signaling. To investigate the modulation of ASC-loaded recombinant human collagen-based microspheres, on the electrophysiological behavior of neonatal rat ventricular myocytes (NRVM). Unipolar extracellular electrograms, derived from microelectrode arrays (8x8 electrodes) containing NRVM, co-cultured with ASC or ASC loaded microspheres, were used to determine conduction velocity (CV) and conduction heterogeneity. Conditioned medium (Cme) of (co)cultures was used to assess paracrine mechanisms. Microspheres did not affect CV in control (NRVM) monolayers. In co-cultures of NRVM and rASC, hASC or pASC, CV was lower than in controls (14.4±1.0, 13.0±0.6 and 9.0± 1.0 vs. 19.5±0.5 cm/s respectively, p